ABSTRACT Optical coherence tomography (OCT) is an optical imaging modality that can perform micron scale, tomographic cross-sectional imaging of microstructure in biological tissues in situ and in real time. Due to the high axial resolution, OCT is ideally suited for imaging tissues with a laminar structure, such as the retina. Recent advances in OCT technology over the past 5 years have enabled dramatic advances in OCT imaging speed and sensitivity. Importantly, high-speed OCT enables rapid volumetric imaging, and facilitates new sources of contrast such as Doppler and spectroscopic OCT. A central goal of this proposal is that the advances in OCT technology will enable depth-resolved, quantitative hemodynamic and metabolic measurements during functional activation in the brain with high spatiotemporal resolution. This proposal will develop novel technologies and methods to enhance the capability of OCT to quantitatively measure blood flow, blood volume, hematocrit, oxygen saturation, and capillary dilation. These technologies and methods will be applied to study neurovascular coupling and oxygen consumption during somatosensory activation. The specific aims of this program are: 1. Develop high-speed OCT microscope platforms for brain imaging. Two spectral / Fourier domain OCT microscope platforms, one operating at near-infrared wavelengths and the other operating at visible wavelengths, will be developed. 2. Develop and validate methods of measuring of blood flow, blood volume, hematocrit, oxygen saturation and capillary dilation with OCT. Methods of quantitatively measuring cortical hemodynamics will be developed. These methods will be validated in vitro in circulating whole blood samples, and in vivo by comparison with two photon microscopy and optical intrinsic signal imaging (OISI). This aim will characterize the performance of OCT relative to other imaging technologies used for measuring cortical hemodynamics. 3. Characterize the laminar response and quantify oxygen consumption during functional activation. The methods developed in Aim 2 will be used to characterize the cortical hemodynamic response according to vascular compartment and cortical layer, and to quantitatively measure oxygen consumption during somatosensory activation. The results of this program will answer fundamental questions about the hemodynamic and metabolic responses at the microscopic level, which will aid interpretation of macroscopic measurements such as BOLD fMRI and improve understanding of cerebrovascular physiology and pathology.